Preliminary studies from our laboratories suggest two stages in the pathology of scleroderma: (a) the cellular stage consisting of mononuclear cellular infiltrates and deposition of reticulin fibers, presumably Type III collagen; and (b) the fibrotic stage characterized mainly by the deposition of Type I collagen. The amounts of Type I and Type III collagens will be determined in the dermis and subcutaneous tissue from normal and scleroderma skin. Fibroblasts will be cultured from upper and lower levels of the skin to determine rate of collagen synthesis and the ratio of Type III to Type I collagens. Type I and Type III collagens will be obtained by limited pepsin digestion, salt fractionation and will be separated by CM-cellulose chromatography and by SDS-acrylamide gel electrophoresis. Distribution of Type I and Type III collagen in scleroderma skin will be studied by indirect immunoelectron microscopy with ferritin-labeled antibodies.